Dextran has been used as an expander of plasma volume for several years. Dextran-70 and 40 preparations, with molecular weights of 70 and 40 kDa, were recommended to manage shock or impending shock caused by hemorrhage, burns, and trauma [2, 3, 6]. Kam et al. [7] used dextran-40 in vitro to evaluate the effect of hemodilution on the coagulation profile, where the thromboelastometry and multiple electrode aggregometry methods measured the test samples. The use of albumin as an alternative might be beneficial in patients suffering from septic shock; however, the cost of clinical-grade albumin is high. Therefore, Bentzer et al. [8] investigated the effects of using dextran-70 on organ failure or mortality in patients suffering from severe sepsis or septic shock. Researchers performed their study using a group of patients with severe sepsis or septic shock admitted to a hospital intensive care unit between 2007 and 2015 and administered dextran-70 for resuscitation. The report concluded that no evidence could be detected to support an unfavorable effect of the use of dextran-70 on organ failures and or mortality in patients with septic shock or severe sepsis [8].

For plasma expansion, alternatives to albumin include crystalloids (normal saline 0.9% sodium chloride and Ringer’s lactate), plasma protein fraction (alternate protein colloids), and dextran (nonprotein colloids). Although nonprotein colloids and crystalloids have not exhibited a benefit over using albumin, these are low-cost options. Dextrans are added to normal saline as an isotonic medium when used as an element in colloid solutions. Winkler mentioned in a previous article on albumin and related products that Rescueflow, a hypertonic mixture, is limited to its prehospital use in treating hypotension caused by bleeding, although its benefit remains uncertain [9]. Warden discussed in his article on fluid resuscitation and early management that in young pediatric burn patients with major burn injuries, colloid replacement is frequently required; thus, the serum protein concentration decreases rapidly during burn shock. In such cases, dextran colloid is routinely used during the resuscitation of children with major burn injuries [10]. Important types of dextran have been summarized in Table 1 (Ref. [11, 12]), indicating their molecular weights and applications in blood transfusions.

Dextrans are used as volume expanders, as they have an effect of inhibition on the aggregation of thrombocyte and coagulation factors. The dextrans infusion can direct to anaphylactic reactions in mothers, which can make the embryo vulnerable. It has been suggested that the anaphylactic reactions can be lowered by administering Hapten–Dextran (Dextran-1 of a low molecular weight preparation of specifically 1.0 kDa) immediately before an infusion using main dextran. The binding of dextran-reactive antibodies to dextran-1 prevents the occurrence of large immune complexes and, subsequently, an immune response [13].

Researchers have investigated the characteristics of dextran polysaccharides in studies relevant to hematology. Dextran-40 has been tested for use in hemodilution compared with normal saline. Kam et al. [7] reported the in vitro effect of hemodilution evaluation on the coagulation profile by dextran-40, which was determined by thromboelastometry and multiple-electrode aggregometry. Researchers used blood samples taken from the veins of 20 volunteers who were in good health. Samples were diluted using dextran-40, or 5%, 10%, and 15% saline solutions; the results of this study for the coagulation profile did not show any platelet dysfunction. Clot formation was significantly impaired by hemodilution with dextran-40 compared to hemodilution with saline and in blood samples without dilution. At these concentrations of hemodilution performed in vitro to exhibit the clinical use of dextran infusions, no considerable fibrinolysis or platelet inhibitions were observed [7].

Studies have been performed to compare the effect of dextran and albumin on blood coagulation in patients undergoing gynecological surgeries. Their platelet count, standard coagulation tests based on plasma, and whole blood viscoelastic clot structure were reported to be highly affected by dextran-70 (6%) compared to albumin (5%); however, the aggregation of platelets did not change. Sigurjonsson et al. [14] reported that the Von Willebrand function was not deranged by isovolumic substitution of dextran-70 more than by albumin (5%) because dextran is hyper-oncotic compared to the 5% solution of albumin and, therefore, it induces a greater expansion in plasma volume and produces a higher dilutional coagulopathy.

A study on dextran deposition in tissues revealed that infused dextran was mainly unchanged when eliminated at a rate of 50% by the kidney within 24 hours of infusion and another 20% in the next 48 hours. Some of the residual 30% dextrans are metabolized by dextranase (6-$\alpha$-D-glucan 6-glucanohydrolase) from the splenic and hepatic sources, while some are eliminated by the gastrointestinal tract after its hydrolysis by coliform bacteria [11]. In a clinical project, biopsy and autopsy studies were conducted using 32 patients treated with regular hemodialysis for about 61 months. These patients had also received plasma expanders in the form of dextran-40 because of the hypotension caused during the hemodialysis process.

The clinical performance of dextran was studied in a control test group of 11 hemodialyzed patients receiving alternative plasma expanders instead of dextran. In the other 11 patients in the dextran test group, who were given the maximum dosage of 0.38 g/kg per week of dextran-40, particles were detected in the macrophage cytoplasm of their various organs. These particles presented positive results in the periodic acid–Schiff (PAS) staining method, which detects dextran. None of the intracellular dextran particles were tested in the control group patients (receiver of an alternative for dextran), while no inclusions were also found in those patients who received a lower dose of dextran-40 below 0.08 g/kg per week. A linear relation was observed between the dextran-40 dosage and the number of inclusion particles. This study demonstrated that the material verified in the macrophages was dextran, structurally modified by macrophage activity to a water-insoluble particle form. Hence, dextran-40 at a lower dose is equally effective without its particle inclusion as other plasma-extender options [11].

Products of dextran polysaccharides with different molecular specifications have established several applications in the pharmaceutical industry. Dextrans of analytical quality are available commercially as active pharmaceutical ingredients (API). They are applied as excipients for the final formulation of clinical drug products, for medical devices, and for the production of solutions used in injections and infusions. Dextran is an inert material formulated with an active drug ingredient for the long-term stabilization of a medication. Dextran is also used as a bulking agent to increase the mass of those specific solid medicine formulations that contain the main active ingredients in very small measures in the ensemble weight of the product [15]. The role of dextran in pharmaceutical products is to act as a diluent—a filler—and to deliberate a medicinal improvement in the final dosage form of an active component in a pharmaceutical preparation.

Dextran is used as a critical constituent of hydrogels for biomedical applications, including in biosensor materials, drug delivery devices, and tissue engineering scaffolds. Dextran has applications as a pro-drug and in many classes of drug delivery vehicles, such as microspheres and nanocarriers. Injectable hydrophilic dextran/AgNP nanocomposite products have been prepared as white light-active biomolecules for their application as an antitumor agent [16].

Dextrans have established their varied applications for analytical purposes, e.g., in the gel filtration process used to separate pharmaceutical compounds [5, 17]. Dextran polymers can be easily cross-linked and fabricated to generate beads, which are required for their use in columns prepared for gel filtration. A commercialized filtration gel based on dextran is Sephadex®, which is available in many bead sizes and porosities, possessing characteristic ranges for molecular weight fractionation. Such filtration gels have multiple applications in analytical examinations, e.g., Sephadex® G-200, with the highest porosity, is suitable for fractionating proteins in the molecular weight range of 4.0 kDa to 80 kDa. In contrast, Sephadex G-25 is specifically useful for separating peptides with molecular weights lower than 5 kDa. Other than neutral dextran gels, some dextran derivatives, such as quaternized and carboxymethyl dextrans, are also commercially available, which are required for anion and cation-exchange chromatography [17].

Dextrans, with their hydrophilic features, have been applied in the conjugation of bioactive substances (such as enzymes, drugs, antibodies, and hormones) to extend their circulation lifetime, increase stability in vivo, or depress their antigenicity. Dextran nanoparticles have been applied in conjugation with insulin for oral insulin administration. Dextran nanocarriers protect insulin from degradation in the gut and modulate its release profiles. In addition to being a hydrophilic and functional polymer, dextrans are extensively used to modify surfaces to fabricate a biosensor. A dextran layer on sensor chips helps minimize the nonspecific adsorption of analytes and facilitates surface immobilization of ligands, thereby successively improving the biosensors’ sensitivity.

Derivatives of different polymer lengths of dextran [18] have many biological applications, such as an antithrombotic agent, in MRI contrast components and drug delivery systems due to its unique benefits of solubility and non-immunogenicity. Several dextran-based drug delivery systems with required design properties, such as nanocarriers and self-assembled micelles, have been created. Because of the high solubility of dextran nanocarriers in water, the solubilization and permeation of drugs are facilitated across the gastrointestinal membrane. Dextran polysaccharide molecules also protect drug molecules against their chemical or enzymatic degradation in the gastrointestinal tract, meaning they can only be depolymerized by a specific enzyme, dextranase. The neutral nature of dextran proves favorable in its protection from the mucus layer, which is negatively charged [19].

Two commonly co-administered drugs for chemotherapy in a wide range of cancers are doxorubicin (DOX) and cisplatin (CIS). Dextran-based self-assembled nanovesicles were prepared to conjugate anticancer drugs DOX and CIS in their core and layer [20]. Further, responsive biopolymer-based microgels/nanogels have been suggested for drug delivery applications [21]. The stability of nanovesicles against the glutathione detoxification was due to dextran vesicular geometry. These had adequate entrapment efficiency and were submitted for breakdown by lysosomal esterase enzyme for the delivery of drugs. In another study, dextran was modified with a 3-pentadecyl phenol to add stimuli-responsive characteristics for pH and enzyme. The anticancer drug doxorubicin could be effectively delivered under acidic pH conditions with the assistance of self-assembled and dual-responsive characteristics of dextran nanovesicles. A different type of derivative, curcumin-functionalized poly (lactic-co-glycolic acid)-dextran nano-micelles, has been synthesized, which exhibited the self-assembled behavior and natural antibacterial activity of curcumin [22]. Table 2 summarizes some commercially available dextrans as active pharmaceutical ingredients for human vaccine applications, lyophilization, organ preservation, and blood volume expanders.

Dextran has many applications in nanomedicine. Dextran nanoparticles have better water solubility, higher load capacity, and inherent viscosity. Thus, these features of dextran made it a favorable polysaccharide material for applications in nano-drug carriers, cell imaging systems, and the fabrication of nano biosensors [23]. For several in vivo applications, dextran is one of the most effectively used polysaccharide-based polymers. Dextran-coated superparamagnetic iron oxide nanoparticles are clinically applied as contrast agents in magnetic resonance imaging, and they also possess cancer nodal staging capabilities. The introduction of a carboxymethyl group can upgrade the functionality and stability of dextran-coated magnetic particles cross-linked to epichlorohydrin to obtain cross-linked iron oxide particles, which have better stability than dextran-coated superparamagnetic iron oxide nanoparticles of the same dimensions [24].

Dextran of different molecular weights and branching configurations has become of commercial and pharmaceutical importance for such a wide range of applications. Therefore, several researchers have studied its biosynthesis using enzymes obtained from specifically selected microbial agents. Some of the methods studied for its enzymatic biosynthesis are discussed in Sections 4 and 5.